Abstract Brain tumors are the leading cause of death from solid tumors in children, but remain a rare disease with a prevalence of approximately 21,000 children and with 2,200 new cases diagnosed in children (<20 y) each year. Tumor staging, detecting recurrent tumor, and assessing response to therapy are critical in the treatment of brain tumors, but current imaging methods have limitations in providing such information. The objective of this study is to validate 32-deoxy-32-[F-18] fluorothymidine (18F-FLT) as an imaging agent to assess cellular proliferation in brain tumors in children and to demonstrate its utility for grading tumors at diagnosis, for accurate identification of tumor recurrence, and for early assessment of response to chemotherapy. 18F-FLT uptake in brain tumors measured by positron emission tomography (PET) will be correlated with histopathology of tumor specimens and with patient outcomes. The proposed studies will evaluate 18F-FLT-PET by testing three hypotheses: 1. 18F-FLT uptake is an accurate marker of cellular proliferation and tumor grade in central nervous system tumors in children. This hypothesis will be tested in children imaged before surgical resection of newly diagnosed central nervous system tumors. Histopathological measures of proliferation will be correlated with the 18F-FLT-PET results. 2. 18F-FLT uptake is an accurate marker cellular proliferation in children with possible recurrent central nervous system tumors. Therefore post-treatment uptake and changes in uptake during therapy may provide discrimination between recurrent tumor and benign tissue. This hypothesis will be tested in children in whom standard imaging has raised concern for tumor recurrence. 18F- FLT-PET results will be compared to histopathological measures of proliferation and to final pathological diagnosis. 3. Changes in 18F-FLT uptake demonstrate the cellular response to chemotherapy and predict clinical outcome in children receiving chemotherapy for treatment of a central nervous system tumor. To test this hypothesis, children undergoing chemotherapy for recently diagnosed central nervous system tumors will be studied by 18F-FLT-PET before chemotherapy and soon after the start (within two months) of chemotherapy. Post-therapy 18F-FLT uptake and changes in 18F-FLT uptake will be correlated with patient outcomes. Although pediatric central nervous system tumors are rare, they are a significant contributor to morbidity and mortality in children. This interdisciplinary project aims to validate and characterize the use of 18F-FLT-PET to evaluate these tumors, which, in turn, is expected improve disease management and enhance the care of children afflicted with brain tumors.